Nerve repair: Regeneration in spinal-cord injury

The spinal cord is the body’s information super highway, constantly buzzing with electro-chemical signals between the brain and the rest of the body. This precious bundle of nerve fibres runs through a cavity within each vertebra. This protects the cord along its length but even this bony armour can’t protect the spinal cord from the worst injuries. With enough force, this delicate cord can get damaged, cutting off all communication to and from the body below the injury site, leaving a patient paralysed. This devastating injury happens to an estimated half a million people each year across the globe. To make things worse, the damage is irreversible. Neurons of the central nervous system don’t seem to be able to regrow their axons: the long, spindly projections that link them to other neurons. Scientists are currently working to understand why these injured nerves can’t repair themselves and re-grow their axons. At the same time, researchers are trying to reboot the regeneration process. So far, most of the research has been done on rodents with researchers using three broad approaches to try to tackle the problem… The first strategy is to change the environment swirling around the damaged nerves to make it more growth friendly by dialling down chemicals that inhibit the ability of nerves to regenerate. One set of molecules that are suspected of blocking regeneration are called chondroitin sulphate proteoglycans (CSPGs). Scientists have shown that by using an enzyme called chondroitinase they can change the structure of the CSPG molecules so that they no longer block the growth of axons. The second strategy is to introduce factors that work directly on the cellular machinery of the damaged neurons to boost their capacity to heal themselves. For example, researchers are trying to make the neurons more receptive to pro-growth signals from their neighbours. Receptor molecules called integrins seem to disappear as neurons mature so researchers are looking for ways to smuggle integrins back into damaged neurons. Researchers are also experimenting with adding in the growth factors themselves. For example, proteins IGF1 and Osteopontin, have again been shown to spark axon regrowth. A third strategy has the potential to combine many aspects of the first two. A study in rats has shown that mesenchymal stem cells (or MSCs) naturally home in on the site of injury and protect against secondary damage caused by the immune system. They also appear to promote axon regeneration, repair damage to the axon’s insulating layer of myelin, and may be able to directly transform into new neurons. A small trial using MSCs in humans was completed last year and the results are due to be reported soon. It’s likely that a successful therapy will involve a combination of these ideas, hopefully giving patients with spinal cord injuries a brighter future.

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